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Gene expression profiling and endothelin in acute experimental pancreatitis
Helieh S Oz1, Ying Lu, Louis P Vera-Portocarrero
1Department of Physiology, College of Medicine, University of Kentucky Medical Center, Lexington, KY 40536, United States. hoz2@email.uky.edu
World Journal of Gastroenterology
|September 13, 2012
Summary
Endothelin receptor antagonists effectively reversed hypersensitivity in experimental pancreatitis by targeting upregulated endothelin-1. Candidate genes identified may aid future diagnosis and gene therapy for inflammatory pain.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Dibutyltin dichloride (DBTC) induces acute pancreatitis and associated pain via reactive oxygen species.
- Gene expression profiling in spinal cord and dorsal root ganglia (DRG) is crucial for understanding pain mechanisms.
Purpose of the Study:
- To analyze gene expression profiles in experimental pancreatitis.
- To investigate the functional reversal of hypersensitivity using endothelin-1 antagonists.
Main Methods:
- DBTC-induced pancreatitis model in Lewis rats.
- Transcriptional profiling using cDNA microarray.
- Treatment with endothelin (ET) receptor antagonists (ET-A BQ123, ET-B BQ-788).
- Assessment of pain behaviors and immunohistochemical analysis of ET-A and ET-B receptors.
Main Results:
- Pancreatitis led to significant changes in spinal cord gene expression, with over 260 upregulated and 60 downregulated genes.
- Endothelin-1 (ET-1) was among the upregulated genes.
- ET-A and ET-B receptor expression increased in DRG neurons and glia.
- ET receptor antagonists significantly reduced pain hypersensitivity without affecting normal behavior.
Conclusions:
- Endothelin receptor antagonists offer protection against inflammatory pain.
- Candidate genes identified can serve as potential biomarkers for diagnosis and targeted gene therapy.
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